BLU-808 Advanced Drug Monograph

BLU-808 Medication Report

Name: BLU-808 Name (English): BLU-808

Mechanism of Action: BLU-808 is an investigational, highly potent and selective oral inhibitor of wild-type KIT (tyrosine kinase). Wild-type KIT plays a central role in mast cell activation. By inhibiting KIT, BLU-808 aims to reduce mast cell activity.

Developer: Blueprint Medicines

Development Stage: Phase 2 clinical trials are planned or ongoing.

Potential Uses: BLU-808 is being investigated for the treatment of various mast cell disorders and allergic/inflammatory conditions, including:

• Chronic Spontaneous Urticaria
• Chronic Inducible Urticaria
• Allergic Rhinoconjunctivitis
• Allergic Asthma
• Mast Cell Activation Syndrome

Phase 1 Clinical Trial Data (Healthy Volunteers):

• BLU-808 was well-tolerated at all doses tested.
• No serious adverse events, discontinuations, or dose modifications due to adverse events, and no significant changes in laboratory measures were observed.
• Demonstrated dose-dependent serum tryptase reductions exceeding 80%, indicating mast cell target engagement.
• Exhibited a half-life supporting once-daily oral dosing and sustained target coverage across a range of doses.

Observed Adverse Events (Phase 1 Healthy Volunteer Trial):

• No treatment-emergent adverse events greater than Grade 1 were reported in the multiple-ascending dose cohorts (1-12 mg once daily).

Ongoing/Planned Clinical Trials:

• Phase 2: Evaluation of safety, tolerability, and clinical activity in Chronic Inducible Urticaria and Chronic Spontaneous Urticaria (NCT06931405).
• Phase 2a: Randomized, double-blind, placebo-controlled study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity in participants with ragweed-induced allergic rhinoconjunctivitis (NCT06922448).
• Phase 1: Completed study evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics, and assessing drug-drug interaction with a CYP3A substrate and the effect of food in healthy adult subjects (NCT06948032).

Preclinical Data Highlights:

• Demonstrated best-in-class selectivity and potency profile in vitro.
• Led to dose-dependent inhibition and depletion of mast cells in multiple in vivo studies.
• Improved lung function in an ovalbumin-induced asthma model in rodents.
• Inhibited human CD34+ derived mast cell degranulation and survival.
• Showed potential to inhibit airway hyper-responsiveness in a preclinical rodent model of allergic asthma.

Note: BLU-808 is an investigational drug and its safety and efficacy have not been established in humans for any indication. The information provided is based on available press releases and clinical trial registry data as of May 13, 2025.